PROJECT SUMMARY: This application is a competing renewal for an Institutional Ruth L. Kirschstein NRSA on the "Genetic Aspects of Alcoholism." The objective of this training program is to provide high level predoctoral and postdoctoral research training on various aspects of the genetics of alcoholism. The main focus of the research training is on the genetic, biological and molecular basis of high alcohol drinking and seeking behavior. Major topics of research include neuronal mechanisms underlying high alcohol-drinking and -seeking behavior;the genetics (including microarrays and QTL) of alcohol metabolizing enzymes, and alcohol preference in selectively bred rodent lines;studies of factors that regulate the expression of genes relevant to alcoholism;analysis of the extent that genetically-influenced biobehavioral factors such as disinhibition-impulsivity and acute tolerance contribute to alcoholism risks in human populations;the use of the alcohol clamp method to assess the effects of genetics on electrophysiologic and subjective response to alcohol;effects of genetics and alcohol drinking on protein expression in selectively bred rodent lines;convergent functional genomic approach toward identifying candidate genes underlying alcoholism;neuropsycho-pharmacological and neuroimaging studies on alcohol craving in humans and rodents;comorbidity of alcohol addiction and schizophrenia in rodent models;and neurodevelopmental abnormalities of fetal alcohol syndrome in rodent models. The rationale for the research training program is that we do not understand how genetics influence alcohol drinking behavior;this is a very important topic and the field needs additional highly trained research investigators. In addition, our program offers translational research training, encompassing both human and animal studies. The program is designed to give the trainee exposure to and participation in high-powered research projects in which state-of-the-art methodologies are used. We expect to support 7 predoctoral trainees (after their first 2 years of study), and 3 postdoctoral trainees (with 0-1 year of experience). We anticipate supporting trainees for at least 3 years (some predoctoral trainees may take 1 or 2 additional years). RELEVANCE: There is convincing evidence that alcoholism runs in families. Identifying the genes that contribute to alcoholism, and understanding how these genes influence neuronal functions would greatly contribute toward understanding and treating alcoholism.